Allopurinol

 

Allopurinol works to reduce elevated uric acid levels, and the intravenous route is designed for chemotherapy patients who cannot tolerate the oral drug route.

Overview

Intravenous allopurinol is designed to reduce or prevent high uric acid levels in the blood in patients who are undergoing chemotherapy treatment for cancer. It works by inhibiting the chemical reactions which occur in the body to produce uric acid.

Excessive levels of uric acid in the body can lead to gout and kidney stones. If left untreated, kidney stones can do permanent damage to the kidneys and lead to kidney failure. Since certain types of chemotherapy treatments, such as those which treat solid tumor malignancies, leukemia, and lymphoma, can lead to an increase in uric acid, allopurinol may be administered to prevent this process and avoid further health complications.

Allopurinol is available in oral and intravenous routes. Although many patients can respond well to the oral route, for some this route is not tolerable. For example, those with tumor lysis syndrome or acute uric acid nephropathy are unable to take oral allopurinol. The intravenous route has proved to be highly effective in preventing or reducing uric acid levels in such patients. Research has found that the intravenous drug can increase uric acid levels in 93% of adults and 92% of children with minimal toxicities, which demonstrates that it is just as safe and effective as the oral route.

In the US, allopurinol is available under the following brand names:

  • Aloprim
  • Lopurin
  • Zyloprim

Condition(s) treated?

  • Hyperuricemia

Type of medicine?

  • Xanthine oxidase inhibitor

Side Effects

Research into the safety of intravenous allopurinol found that of 1,378 patients, 125 reported a total of 301 adverse reactions to the drug. However, many of the patients were taking multiple medications concurrently and were being treated for advanced stages of cancer. Only 19 patients reported side effects which could be directly attributed to allopurinol.

Of those 19 patients, 15 adverse reactions were allergic. They experienced either a rash, a reaction at the local injection site or a high white blood cell count which is indicative of allergic reaction. Although rashes may seem like relatively minor side effects they can be fatal and should be reported to a doctor immediately. The intravenous administration of allopurinol should be stopped immediately.

One individual reported severe diarrhea while undergoing therapy with allopurinol, while another experienced nausea. One patient reported decreased renal function, and another experienced a seizure; intravenous allopurinol was a possible cause of these side effects, although the patients were also undergoing other treatments.

Other possible side effects of intravenous allopurinol, which could be dangerous and should be reported to a doctor urgently, include:

  • Pain or bloating in stomach or abdomen
  • Bladder pain
  • Vomiting of blood
  • Black, tarry stools or dark urine
  • Burning or painful urination or difficulty urinating
  • Unusually frequent urge to urinate
  • Clay-colored stools
  • Cloudy urine
  • Blood in urine or stools
  • Bleeding gums
  • Coughing blood
  • Cough, sore throat or hoarseness
  • Difficulty swallowing
  • Difficulty speaking
  • Blurred vision or double vision
  • Yellow eyes or skin
  • Swollen glands
  • Dilated neck veins
  • Tightness in the chest
  • Chest pain
  • Labored or irregular breathing or rapid, shallow breathing
  • Wheezing
  • Chills
  • Fever
  • Dizziness or lightheadedness when standing up
  • Fainting
  • Fast, slow or irregular heartbeat
  • Extreme fatigue
  • Muscle pain or weakness
  • Inability to move the arms, legs, or facial muscles
  • Pain, stiffness, or swelling in joints
  • Numbness, tingling or pain in the hands or feet
  • Swelling or pain in feet or legs
  • Inability to speak
  • Increased menstrual flow or unusual vaginal bleeding
  • Increased sweating
  • Itching
  • Loosening of the fingernails
  • Loss of appetite
  • Pain in lower back or side
  • Nosebleeds
  • Changes in skin color
  • Pinpoint red spots on the skin
  • Prolonged bleeding from cuts
  • Unusual bleeding or bruising
  • Redness of the face, neck, arms, and upper chest
  • Sores, ulcers, or white spots on mouth or lips

There have also been rare reports of alopecia, indigestion, and drowsiness when undergoing allopurinol therapy, but these side effects don’t usually require medical attention.

Dosage

Intravenous allopurinol can only be administered by a trained healthcare professional, such as a doctor or nurse. It is only administered in a hospital and this process often takes place in advance of chemotherapy sessions.

It is helpful to drink lots of fluids while undergoing allopurinol treatment, as this can help to flush excess uric acid from the kidneys to reduce the risk of kidney stones. Doctors may advise on how much water to drink each day while you are receiving allopurinol. It is generally recommended that patients consume enough fluid that they produce at least two liters of urinary output daily, with neutral or slightly alkaline urine.

Recommended dosages

The daily dosage of allopurinol given will vary from patient to patient and may depend on the severity of their uric acid levels and the type of chemotherapy treatment they are undergoing. Doctors usually use the patient’s serum uric acid (levels of uric acid in blood) as an index to decipher appropriate dosage. In patients with preexisting liver disease, impaired renal function and certain concurrent illnesses such as diabetes and hypertension, further tests are usually performed to decide on the safest, most effective dosage of allopurinol.

In adults, the recommended dose ranges between 200 and 400 mg/m2/day, with the maximum dose being 600 mg/m2/day. Doses exceeding 600 mg appear to be no more effective. For children, dosage starts at 200 mg/m2/day and should be adjusted after monitoring of the patient.

For patients with impaired renal function, creatinine clearance is used to determine dosage. If creatinine clearance is between 10 and 20 mL/min, 200mg/day is recommended. At 3 to 10 mL/min creatinine clearance, 100 mg/day is recommended. If creatinine clearance is less than 3 mL/min, 100 mg is usually administered but with longer intervals between injections.

Administration of allopurinol injections

For the best results, allopurinol therapy should begin between 24 and 48 hours before chemotherapy starts. Daily doses of allopurinol can be administered as single infusions, or they can be divided equally between multiple infusions spaced six, eight, or twelve hours apart.

Allopurinol is provided to healthcare providers in powder form and is reconstituted into a solution for injection. The powder is stored in single-use 50 mL vials. It is first dissolved with 25 mL of sterile water, before being diluted to a suitable concentration with 0.9% sodium chloride or 5% dextrose. The final concentration of allopurinol should not exceed 6 mg/mL.

Interactions

The following drugs have been identified as ones which interact with allopurinol. The interactions may increase the risk of side effects, lead to health complications, or cause either one of the drugs to become more or less potent. If you are already receiving one of the drugs listed below, your doctor may choose not to administer allopurinol, or they may adjust your other prescriptions and dosages.

  • Mercaptopurine/Azathioprine
  • Dicumarol
  • Uricosuric Agents
  • Thiazide Diuretics
  • Ampicillin/Amoxicillin
  • Cytotoxic Agents
  • Chlorpropamide
  • Cyclosporine

Warnings

Decreased renal function and allopurinol

Patients with decreased renal function should be given lower doses of allopurinol. This is because the kidneys will process the drug at a slower than normal rate, which will leave the drug in the body for longer and thus increase the effects of it. When a patient with reduced renal function is first prescribed intravenous allopurinol, they should be carefully observed in order that the dose can be adjusted where necessary after monitoring renal function.

In instances where patients have severe renal function impairment, the lowest effective dose is administered to reduce the risk of side effects. Doctors may also choose to increase the normal interval between doses.

Pregnancy and allopurinol

Allopurinol sits within pregnancy category C, which means that the drug could pose a risk to the fetus. Only animal tests have been performed on the fetal effects of the drug, and no adequate or well-controlled studies have been conducted on pregnant women. This is because women of reproductive age are less likely to require allopurinol therapy, which means data on the topic is scarce. Since the fetal effects are unknown, the FDA states that the drug should be used with caution during pregnancy and only if the potential benefits of the drug outweigh the potential risk to the fetus.

In regard to breastfeeding, caution must be exercised when considering the administration of allopurinol. It is known that allopurinol can be excreted in breast milk, but it is not clear what effect this may have on a nursing infant. As with administering allopurinol during pregnancy, it should only be done if the benefits of the drug for the mother far outweigh the potential risks to the child. In most cases, it would be preferable to avoid breastfeeding while undergoing allopurinol therapy.

Storage

Allopurinol is provided in powder form and must be reconstituted and diluted before injection. It is provided in single-use, 50 mL flint glass vials which contain the equivalent of 500 mg of allopurinol. These vials should be stored in an environment where the temperature can be controlled between 20° to 25°C (68° to 77°F).

Once the powder allopurinol has been made into a solution, it should be stored at 20° to 25°C (68° to 77°F) and used within 10 hours. It should not be refrigerated. If unused during this time, the solution should be appropriately disposed of.

Summary

Allopurinol (intravenous route) is a xanthine oxidase inhibitor which works to reduce uric acid levels in the blood in patients who are undergoing chemotherapy treatment for cancer. Excessive uric acid levels can lead to gout and kidney stones, and in the worst cases can cause kidney failure. By starting allopurinol therapy between 24 and 48 hours before chemotherapy, it is possible to prevent high uric acid levels and to reduce uric acid in those who have already proven to have elevated levels of the substance in their blood.

Although allopurinol can be administered orally, some patients cannot tolerate the oral drug route due to other health complications. Intravenous allopurinol was developed for patients with conditions such as tumor lysis syndrome or acute uric acid nephropathy, where the use of oral allopurinol is simply not suitable. Research has found allopurinol injections to be just as safe and effective as the oral route.

The most common side effect associated with allopurinol is allergic reaction to the drug. A rash, lesions, and swelling of the tongue, lips, throat, and face are all indicative of an allergic reaction. In these instances, symptoms should be reported to a doctor and administration of allopurinol injections should be stopped immediately.

Dosage of allopurinol varies between 200 mg and 400 mg each day, with the maximum dosage being 600 mg. Patients with renal impairment should be administered lower dosages and carefully monitored throughout the treatment. The injection can only be administered by healthcare professionals such as doctors and nurses

Resources
Last Reviewed:
December 10, 2017
Last Updated:
December 22, 2017